出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/15 12:00:59」(JST)[Wiki en表示]
|Systematic (IUPAC) name|
|Oral (film-coated tablets)|
|Bioavailability||~60% (Tmax = 35±5 min)|
|Metabolism||Extensive hepatic (FMO1 and FMO3), primarily N-oxidation|
|Biological half-life||5.7±0.3 hours|
|Excretion||Renal (3.7–4.1% as unchanged itopride, 75.4–89.4% as itopride-N-oxide)|
|CAS Number||122898-67-3 Y|
|Molar mass||358.43 g/mol|
|NY (what is this?)|
Itopride (INN, trade name Ganaton) is a prokinetic benzamide derivative unlike metoclopramide or domperidone. These drugs inhibit dopamine and have a gastrokinetic effect. Itopride is indicated for the treatment of functional dyspepsia and other gastrointestinal conditions.
Itopride is not currently approved by the U.S. Food and Drug Administration (FDA) for use in the United States, nor is it yet approved in the United Kingdom. This may explain the apparent lack of patient information available in English compared to other similar classes of medication.
- 1 Clinical use
- 2 Contraindications and precautions
- 3 Adverse drug reactions
- 3.1 Cardiac studies
- 4 Pharmacology
- 4.1 Pharmacokinetics
- 4.2 Mechanism of action
- 5 Interactions
- 6 Trade names
- 7 See also
- 8 References
- 9 External links
Typically, itopride is indicated in the treatment of GI symptoms caused by reduced GI motility:
- dyspepsia of a non-ulcer/dysmotility type (gastric "fullness", discomfort, and possible pain)
- gastroparesis (delayed gastric emptying)
- nausea and vomiting
- other possible gastric, prolactin, or dopamine related conditions
Itopride is typically taken three times a day. The dose is usually taken on an empty stomach about an hour before meals. However, the dosage and details of administration may vary depending on the patient's age, symptoms, and other factors.
Itopride was shown to significantly improve symptoms in patients with functional dyspepsia and motility disorders in placebo-controlled trials.
These studies concluded that the reduction in the severity of symptoms of functional dyspepsia after 8 weeks of treatment with itopride indicated that itopride was significantly superior to placebo and that itopride yielded a greater rate of response than placebo in significantly reducing pain and fullness.
Contraindications and precautions
Itopride is a relatively new drug and it is not currently approved for normal prescribed use nor OTC use in either the US nor the UK. However, this does not necessarily indicate that itopride is not effective or safe.
Patients taking itopride should report any side-effects to their treating physician.
Itopride is contraindicated in hypersensitivity to itopride or benzamides; lactation, GI hemorrhage, obstruction or perforation. Itopride may not be indicated for those suffering from Parkinson's disease or other conditions involving dopamine regulation issues. Itopride should be used with special caution in the young and the elderly. Little information is available at this time regarding the safe use of itopride during pregnancy.
Adverse drug reactions
The most common side-effects of itopride include mild to moderate abdominal pain and diarrhoea. Some other side effects that may occur include: rash, giddiness, exhaustion, back or chest pain, increased salivation, constipation, headache, sleeping disorders, dizziness, galactorrhea, and gynecomastia.
Other side effects may also be present.
Leukopenia, a reduction in the normal level of white blood cells, can be a potentially life-threatening reaction to itopride.
Central nervous system adverse effects do not tend to occur due to poor penetration across the blood brain barrier, although a slight raising of prolactin levels may occur. Raising of prolactin levels is more common with high dose regimes of itopride.
Itopride belongs to the same benzamide group as cisapride, a drug found to affect QT interval and possibly predispose those using it to cardiac arrhythmias. However, itopride does not have any adverse effect on the QT interval.
Later, in a study conducted with healthy adult volunteers, itopride was shown as unlikely to cause cardiac arrhythmias or ECG changes in part to the lack of significant interaction and metabolism via the cytochrome P450 enzyme pathway, unlike cisapride and mosapride, as it is metabolized by a different enzyme set. New molecular studies on guinea pig ventricular myocytes also supported the cardiac safety profile of itopride, as it did not affect certain potassium mechanisms that may have been affected by cisapride or mosapride. Moreover, itopride has no affinity for the 5-HT4 receptors, unlike other benzamides such as cisapride and mosapride, which are 5-HT4 agonists. The affinity of cisapride for 5-HT4 receptors in the heart has been implicated in the undesirable cardiac effects of cisapride itself.
The conclusion of this study revealed that itopride is devoid of any abnormal effect on QT interval. Therefore, it may be possible that itopride could be considered as a better and certainly safer prokinetic agent than either cisapride or mosapride, and itopride should also be considered a welcome treatment addition for symptomatic nonulcer dyspepsia and other gastric motility disorders.
There is evidence that itopride may have prokinetic effects throughout the gastrointestinal tract from the stomach to the end of the colon. The pharmacokinetics of itopride appear to differ between Asian and Caucasian populations, with Caucasians having 30-50 percent lower blood levels of itopride after oral administration. Itopride poorly penetrates across the blood brain barrier because of itopride's high polarity and thus itopride does not tend to cause any central nervous system adverse effects. Itopride has no effect on potassium channels.
After oral administration itopride undergoes rapid and extensive absorption with levels of itopride peaking in the blood plasma after only 35 minutes. Itopride is primarily eliminated via the kidneys having an elimination half-life of approximately 6 hours.
Mechanism of action
Itopride increases acetylcholine concentrations by inhibiting dopamine D2 receptors and acetylcholinesterase. Higher acetylcholine increases GI peristalsis, increases the lower esophageal sphincter pressure, stimulates gastric motility, accelerates gastric emptying, and improves gastro-duodenal coordination.
Itopride given as a single dose study found that it also raises levels of motilin, somatostatin and lowers levels of cholecystokinin, as well as adrenocorticotropic hormone. These effects may also contribute to itopride's pharmacology.
Anticholinergic agents reduce the action of itopride. It is worth noting that itopride is a relatively new drug and that it is, therefore, possible that other drugs may interact with itopride, rendering contraindications or side effects that are not currently known.
Itopride is available under the brand names Ganaton ((JP, CZ, RU), Abbott Laboratories), Itomed ((RU, KR, UA, MD), PRO.MED.CS Praha a.s.), Itogard (Apex Pharmaceuticals , Nepal) and others.
- Smith, Dennis A.; Allerton, Charlotte; Kubinyi, Hugo; van de Waterbeemd, Han; Walker, Don K., eds. (April 2012). Pharmacokinetics and Metabolism in Drug Design (3rd ed.). Weinheim: Wiley-VCH. p. 132. ISBN 978-3-527-32954-0.
- "Ganaton (itopride hydrochloride) Tablets 50 mg. Prescribing Information" (PDF). Abbott Japan Co., Ltd. Retrieved 9 December 2015.
- Iwanaga Y, Miyashita N, Saito T, Morikawa K, Itoh Z (June 1996). "Gastroprokinetic effect of a new benzamide derivative itopride and its action mechanisms in conscious dogs". Jpn. J. Pharmacol. 71 (2): 129–37. doi:10.1254/jjp.71.129. PMID 8835639.
- Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C (February 2006). "A placebo-controlled trial of itopride in functional dyspepsia". N. Engl. J. Med. 354 (8): 832–40. doi:10.1056/NEJMoa052639. PMID 16495395.
- Huang, X.; Lv, B.; Zhang, S.; Fan, YH.; Meng, LN. (Dec 2012). "Itopride therapy for functional dyspepsia: a meta-analysis". World J Gastroenterol 18 (48): 7371–7. doi:10.3748/wjg.v18.i48.7371. PMC 3544044. PMID 23326147.
- Chiba, T.; Tokunaga, Y.; Ikeda, K.; Takagi, R.; Chishima, R.; Terui, T.; Kudara, N.; Endo, M.; et al. (Sep 2007). "Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies". Hepatogastroenterology 54 (78): 1878–81. PMID 18019739.
- Keil, R. (May 2004). "[Prokinetics and diabetes mellitus]". Vnitr Lek 50 (5): 358, 360–2. PMID 15305632.
- Holtmann, Gerald; Talley, Nicholas J.; Liebregts, Tobias; Adam, Birgit; Parow, Christopher (2006). "A Placebo-Controlled Trial of Itopride in Functional Dyspepsia". New England Journal of Medicine 354 (8): 832–40. doi:10.1056/NEJMoa052639. PMID 16495395.
- Kim, YS.; Kim, TH.; Choi, CS.; Shon, YW.; Kim, SW.; Seo, GS.; Nah, YH.; Choi, MG.; Choi, SC. (Jul 2005). "Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study" (PDF). World J Gastroenterol 11 (27): 4210–4. PMID 16015691.
- Gupta, Seema; Kapoor, Vinod; Gupta, B. M.; Kapoor, B.; Verma, Ujala; Gupta, Vikram (2005). "Effect Of Itopride hydrochloride on QT interval in adult healthy volunteers" (PDF). JK-Practitioner 12 (4): 207–10.
- Lim, HC.; Kim, YG.; Lim, JH.; Kim, HS.; Park, H. (Jun 2008). "Effect of itopride hydrochloride on the ileal and colonic motility in guinea pig in vitro". Yonsei Med J 49 (3): 472–8. doi:10.3349/ymj.2008.49.3.472. PMID 18581598.
- Stevens, JE.; Russo, A.; Maddox, AF.; Rayner, CK.; Phillips, L.; Talley, NJ.; Giguère, M.; Horowitz, M.; Jones, KL. (May 2008). "Effect of itopride on gastric emptying in longstanding diabetes mellitus". Neurogastroenterol Motil 20 (5): 456–63. doi:10.1111/j.1365-2982.2007.01058.x. PMID 18179609.
- Morisawa, T.; Hasegawa, J.; Hama, R.; Kitano, M.; Kishimoto, Y.; Kawasaki, H. (1999). "Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes". Res Commun Mol Pathol Pharmacol 106 (1–2): 37–45. PMID 11127807.
- Bose, A.; Wong, TW.; Singh, N. (Apr 2013). "Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics". Saudi Pharm J 21 (2): 201–13. doi:10.1016/j.jsps.2012.03.006. PMC 3744972. PMID 23960836.
- Katagiri, F.; Shiga, T.; Inoue, S.; Sato, Y.; Itoh, H.; Takeyama, M. (2006). "Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects". Pharmacology 77 (3): 115–21. doi:10.1159/000093485. PMID 16717477.
- Itopride on www.cimsasia.com
- Abbott Labs "Ganaton"
- "Itopride in Functional Dyspepsia:a Dose Finding Study" at Clinicaltrials.gov
- Molecularly imprinted polymer-based bulk optode for the determination of itopride hydrochloride in physiological fluids.
- Abdel-Haleem FM1, Madbouly A2, El Nashar RM3, Abdel-Ghani NT2.
- Biosensors & bioelectronics.Biosens Bioelectron.2016 Nov 15;85:740-2. doi: 10.1016/j.bios.2016.05.081. Epub 2016 May 26.
- We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1×10(-1)-1×10(-4)molL(-1). In comparison to the optode containi
- PMID 27266658
- Validation of the Leuven Postprandial Distress Scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome.
- Carbone F1, Vandenberghe A2, Holvoet L3, Vanuytsel T4, Van Oudenhove L1, Jones M5, Tack J6.
- Alimentary pharmacology & therapeutics.Aliment Pharmacol Ther.2016 Aug 12. doi: 10.1111/apt.13753. [Epub ahead of print]
- BACKGROUND: A validated patient-reported outcome instrument is lacking for the functional dyspepsia/postprandial distress syndrome.AIM: To validate the Leuven Postprandial Distress Scale (LPDS).METHODS: The LPDS diary, comprising eight symptoms with verbal descriptors rated for severity (0-4), was d
- PMID 27518319
- Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.
- Ito K1, Kawachi M1, Matsunaga Y1, Hori Y1, Ozaki T1, Nagahama K1, Hirayama M1, Kawabata Y1, Shiraishi Y1, Takei M1, Tanaka T1.
- Drug research.Drug Res (Stuttg).2016 Apr;66(4):196-202. doi: 10.1055/s-0035-1564084. Epub 2015 Sep 29.
- Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinest
- PMID 26418413
- 消化器内科 59(6), 574-582, 2014-12
- NAID 40020301655
- Effects of Mosapride Citrate, a 5-HT_4-Receptor Agonist, on Gastric Distension-Induced Visceromotor Response in Conscious Rats
- Journal of pharmacological sciences 116(1), 47-53, 2011-05-20
- NAID 10029893898
- 日本小児外科学会雑誌 46(6), 946-950, 2010-10-20
- NAID 110007817468
- Buy Itopride Hydrochloride (CAS 122892-31-3), an AChE inhibitor and D2DR inhibitor, from Santa Cruz. Purity: >98%, MF: C20H26N2O4 HCl, MW: 394.88 ... アプリケーション： An AChE inhibitor and D2DR inhibitor CAS 番号：
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